Figure 2 | Scientific Reports

Figure 2

From: Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes

Figure 2

Overview of proteomics profiling upon chiglitazar, sitagliptin, and placebo treatments by data-independent acquisition mass spectrometry. (A) Workflow of proteome profiling and data analysis. Plasma sample preparation was performed, and the peptides prepared were injected into the mass spectrometer by applying a data-independent acquisition (DIA) approach. Raw mass spectrometry data were analyzed by applying DIA-MS2pep, Skyline, and the R package iq. After quality control and preprocessing, quantitative proteomics data were used for statistical analysis. (B) A total of 314 proteins were quantified from 471 plasma samples and annotated according to HPA (Human Protein Atlas). Tissue-specific categories and enriched tissue types are distinguished. Represent immune-related proteins and tissue-specific proteins are labeled. (C) Bar plot showing protein abundance variance explained by treatment, blood glucose, lipid metabolism, and demographics (BMI, age, and sex) measured as the Sum of Squares by using multifactor ANOVA (N = 157). The variance caused by blood glucose (HbA1c, PBG, FPG, and FINS) and lipid profiles (HDL-C, LDL-C, FFA, TC, and TG) is shown by the average variance of corresponding clinical variables. (D) Results from multifactor ANOVA based on factors of clinical variables, showing the most highly associated proteins with each factor (N = 157). Example of (E) an HbA1c-associated protein proteoglycan 4 (PRG4), and (F) an HDL-C-associated protein apolipoprotein A1 [APOA1; multifactor ANOVA with Benjamini and Hochberg (BH) correction, adjusted p-value < 0.05, N = 157]. (G) Boxplot showing the protein abundance of the blood glucose- and lipid profile-associated protein gelsolin (GSN) at baseline, week 12, and week 24 in the placebo, chiglitazar, and sitagliptin groups. The asterisks represent the significant degree of change between baseline and week 12 or week 24 (paired t-test; placebo, N = 23; chiglitazar, N = 103; sitagliptin, N = 31). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; ns, no significant difference.

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